A Phase II Study of Increased-Dose Abiraterone Acetate in... | NCT01637402

NCT01637402

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
NCI-2012-02079	Registry Identifier	NCI Clinical Trials Reporting Program (CTRP)

Status Module

Sponsor/Collaborators Module

Name	Class
Janssen Biotech, Inc.	INDUSTRY

Oversight Module

Description Module

Detailed Description

This is a phase II multicenter trial of Abiraterone Acetate (AA) in patients with progressive prostate cancer despite androgen deprivation with a particular focus on the pharmacokinetic, pharmacodynamic, and pharmacogenomic events occurring at the time of apparent drug resistance. All eligible patients will have baseline (prior to taking the first dose of Abiraterone Acetate 1000mg/daily) measures of routine clinical variables along with measurements of baseline and treatment related changes in testosterone, androgen, and endocrine levels, genotyping of single-nucleotide polymorphisms (SNP) in the selected enzymes known to be directly inhibited by Abiraterone Acetate, and collection of circulating tumor cells. All patients will be requested to consent for biopsies which will be performed prior to treatment and at the time of disease progression on standard dose Abiraterone Acetate therapy. These biopsies will be analyzed for expression of an androgen receptor (AR)-signature as well as for microarray analysis to explore changes in methylation, and expression of CYP17A1 and other androgen synthesis genes.

Subjects will then begin daily oral therapy with Abiraterone Acetate 1000mg po daily with physiologic prednisone 5mg BID replacement. No food should be consumed for at least 2 hours before the dose of Abiraterone Acetate and for at least 1 hour after the dose of Abiraterone Acetate is taken. Prostate-specific antigen (PSA) will be followed monthly. Abiraterone Acetate will be supplied by Janssen Services. At the end of the first month, the third month, and then every three months thereafter, Abiraterone Acetate, testosterone, and androgen levels will be followed. Subjects not achieving a greater than or equal to 30% PSA decline at 12 weeks will be taken off study. At the time of progression (defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria as a 25% increase in PSA above the nadir and an increase in the absolute value PSA of at least 2ng/dl or back to baseline confirmed at least 2 weeks afterward) for subjects who achieved an initial greater than or equal to 30% PSA decline (referred to as Progressive Disease (PD) #1), subjects will begin taking Abiraterone Acetate 1000 mg po BID. Patients will continue to take prednisone 5mg twice a day (BID) and will continue this therapy until a second progression at which point they will be withdrawn from the study. While 1000 mg po BID is not the FDA recommended dose, it is the dose to be investigated in this study.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Standard Dose	Experimental	1000 milligrams (mg) abiraterone acetate in combination with prednisone taken once a day until progression defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria	Drug: Abiraterone Acetate Drug: Prednisone
Escalated Dose	Experimental	Participants who progressed on the standard dose will be assigned 1000 milligrams (mg) abiraterone acetate in combination with prednisone taken twice a day for at least 12 weeks until progression as defined by RECIST criteria OR by the Prostate Cancer Working Group 2 (PCWG) criteria	Drug: Abiraterone Acetate Drug: Prednisone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Abiraterone Acetate	Drug	Standard dose participants: 1,000 mg, once daily, oral administration. Dose escalation participants: 1,000 mg, twice daily, oral administration	Escalated Dose

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Patients With PSA Response From Dose Escalation	A PSA response for the dose escalation group is defined as a participant with a documented PSA decline after 12 weeks of therapy with standard-dose, then had disease progression, and then achieved a ≥30% PSA decline after 12 weeks from the start of dose escalation therapy.	Up to 12 weeks from start of dose escalation

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Worst-grade, Treatment-related Toxicities for Dose Escalation Group	Frequency of any treatment-related toxicity with increased-dose Abiraterone Acetate by maximum observed grade will be tabulated for the study cohort. Toxicities will be graded for management according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 as a measure of patient safety.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study
Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
Written Authorization for Use and Release of Health and Research Study Information has been obtained
Male aged 18 years and above
Able to swallow the study drug whole as a tablet
Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken
Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last study drug administration.
Have a baseline serum potassium of ≥ 3.5 milliequivalents per litre (mEq/L)
Have aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels < 1.5 x upper limit of normal (ULN)
Have a serum albumin of ≥ 3.0 g/dL
Total bilirubin ≤ 1.5 x ULN (In patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN is acceptable)
Have a platelet count of ≥ 100,000/μL
Have an absolute neutrophil count of > 1500 cell/mm3
Have a calculated creatinine clearance ≥ 60 mL/min
Have a hemoglobin of ≥ 9.0 g/dL
Have histologically confirmed adenocarcinoma of the prostate.
No prior therapy with chemotherapy for metastatic prostate cancer.
Have metastatic disease based on a positive bone scan or objective imaging on CT scan.
Have ongoing gonadal androgen deprivation therapy with Luteinizing hormone-releasing hormone (LHRH) analogues or orchiectomy. Patients who have not had an orchiectomy must be maintained on effective LHRH analogue therapy for the duration of the trial.
Testosterone < 50 ng/dL.
Progressive disease after androgen deprivation: PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression.
Antiandrogen Withdrawal (AAWD): Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen.
Disease progression after antiandrogen withdrawal is defined as 2 consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression.
For patients receiving flutamide, at least one of the PSA values must be obtained 4 weeks or more after flutamide discontinuation.
For patients receiving bicalutamide or nilutamide, at least one of the PSA values must be obtained 6 weeks or more after antiandrogen discontinuation.
No antiandrogen withdrawal response is expected in patients in whom antiandrogen therapy did NOT result in a decline in PSA or in those patients in whom the response to antiandrogens was < 3 months. Therefore, it is not necessary to wait for AAWD in patients without PSA decline on an anti-androgen or in those in whom a PSA response lasted < 3 months.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Life expectancy of ≥ 12 weeks.

Exclusion Criteria:

Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
Known brain metastasis
Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg) Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment
Active or symptomatic viral hepatitis or chronic liver disease
History of pituitary or adrenal dysfunction
Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
Atrial Fibrillation, or other cardiac arrhythmia requiring medical therapy
Administration of an investigational therapeutic within 30 days of screening
Have poorly controlled diabetes
Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents
Have a pre-existing condition that warrants long-term corticosteroid use in excess of study dose
Have known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients
Any condition which, in the opinion of the investigator, would preclude participation in this trial.
Pure small cell carcinoma of the prostate or any mixed histology cancer of the prostate (eg: neuroendocrine) which contains < 50% adenocarcinoma.
Therapy with other hormonal therapy, including any dose of megestrol acetate (Megace), finasteride (Proscar), dutasteride (Avodart) any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid within 4 weeks prior to first dose of study drug.
Prior therapy with Abiraterone Acetate or other CYP17 inhibitor(s) including TAK-700 or TOK-001, or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer.
Prior therapy with ketoconazole for > 2 weeks for prostate cancer.
Therapy with supplements or complementary medicines/botanicals within 4 weeks of first dose of study drug, except for any combination of the following:
Conventional multivitamin supplements
Selenium
Lycopene
Soy supplements
Prior radiation therapy completed < 4 weeks prior to enrollment
Prior chemotherapy for castration resistant prostate cancer. Patients who have received chemotherapy for early stage prostate cancer (e.g. as part of a neoadjuvant or adjuvant trial) or for other malignancies are eligible provided that >1 year has passed since the administration of the last chemotherapy dose.
Any "currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next year.
Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
Patients in whom urgent chemotherapy, in the opinion of the treating physician, is indicated should not be enrolled in this study.

Contacts/Locations Module

Name	Affiliation	Role
Terence Friedlander, MD	University of California, San Francisco	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Francisco		San Francisco	California	94143	United States
Oregon Health and Science University

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28655452	Result	Friedlander TW, Graff JN, Zejnullahu K, Anantharaman A, Zhang L, Paz R, Premasekharan G, Russell C, Huang Y, Kim W, Aggarwal RR, Lin AM, Fong L, Alumkal JJ, Beer TM, Sharifi N, Alyamani M, Dittamore R, Small EJ, Paris PL, Ryan CJ. High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer. Clin Genitourin Cancer. 2017 Dec;15(6):733-741.e1. doi: 10.1016/j.clgc.2017.05.026. Epub 2017 Jun 3.

IPD Sharing Statement Module

All participants were prescribed the standard dose(STD). Participants who did not exhibit prostate-specific antigen (PSA) decline at 12 weeks were deemed 'primary-resistant' and taken off study. Participants continued STD until progression, at which time, they were assigned to the escalated dose was for a minimum of 12 weeks.

ID	Title	Description
FG000	Standard Dose	Abiraterone 1000 mg once daily Prednisone 5 mg twice daily
FG001	Escalated Dose	Abiraterone 1000 mg twice daily Prednisone 5 mg twice daily

Periods

Title

Milestones

Reasons Not Completed

Standard Dose Regimen

Type	Comment	Milestone Data
STARTED		FG00041 subjects FG0010 subjectsEscalated dose not introduced as treatment option until after Week 12 evaluation
COMPLETED		FG00038 subjects FG0010 subjects
NOT COMPLETED		FG0003 subjects FG0010 subjects

Type	Comment	Reasons
Lack of Efficacy		FG0002 subjects FG0010 subjects
Adverse Event		FG0001 subjects FG001

Week 12 Evaluation

Type	Comment	Milestone Data
STARTED		FG00038 subjects FG0010 subjectsEscalated dose not introduced as treatment option until after Week 12 evaluation
COMPLETED		FG00032 subjects

Treatment Regiments Post Week 12

Type	Comment	Milestone Data
STARTED		FG00014 subjectsPatients continuing on standard dose FG00118 subjectsPatients who progressed after decline on standard dose
COMPLETED		FG0005 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Patients Who Received Treatment	Abiraterone Acetate: Standard dose: 1,000 mg, once daily, oral administration Increased dose offered after week 12 evaluation to participants who progressed after decline on standard dose: 1,000 mg, twice daily, oral administration Prednisone: 5 mg, twice daily, oral administration

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With PSA Response From Dose Escalation

A PSA response for the dose escalation group is defined as a participant with a documented PSA decline after 12 weeks of therapy with standard-dose, then had disease progression, and then achieved a ≥30% PSA decline after 12 weeks from the start of dose escalation therapy.

Posted

Count of Participants

Participants

Up to 12 weeks from start of dose escalation

ID	Title	Description
OG000	Dose Escalation	Dose Escalation (until PSA decrease of at least 30% after 12 weeks): Abiraterone 1,000 mg, twice daily, Prednisone 5 mg twice daily

Units	Counts
Participants

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Standard Dose Therapy	Abiraterone 1000 mg daily, Prednisone 5 mg twice daily

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Atrial fibrillation	Cardiac disorders	CTCAE (4.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Hypertension	Vascular disorders	CTCAE (4.0)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr. Terry Friedlander, MD	University of California, San Francisco	415-514-6380		Terence.Friedlander@ucsf.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 17, 2014	Jul 19, 2019	Prot_SAP_000.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D009369	Neoplasms

Intervention Browse Module

ID	Term
D000069501	Abiraterone Acetate
D011241	Prednisone

ID	Term
D000736	Androstenes
D000731	Androstanes
D013256	Steroids
D000072473	Fused-Ring Compounds

Masking Info

EG0001 affected41 at risk

EG0010 affected18 at risk

EG0005 affected41 at risk

EG0012 affected18 at risk

OG00113.5(3.1 to 44.7)